tbuckley/cabot-search huggingface dataset:
Diagnosis and Treatment of Acute Myocarditis
Authors: Enrico Ammirati, Javid J. Moslehi
Journal: JAMA (2023)

Importance Acute myocarditis, defined as a sudden inflammatory injury to the myocardium, affects approximately 4 to 14 people per 100 000 each year globally and is associated with a mortality rate of approximately 1% to 7%. Observations The most common causes of myocarditis are viruses, such as influenza and coronavirus; systemic autoimmune disorders, such as systemic lupus erythematosus; drugs, such as immune checkpoint inhibitors; and vaccines, including smallpox and mRNA COVID-19 vaccines. Approximately 82% to 95% of adult patients with acute myocarditis present with chest pain, while 19% to 49% present with dyspnea, and 5% to 7% with syncope. The diagnosis of myocarditis can be suggested by presenting symptoms, elevated biomarkers such as troponins, electrocardiographic changes of ST segments, and echocardiographic wall motion abnormalities or wall thickening. Cardiac magnetic resonance imaging or endomyocardial biopsy are required for definitive diagnosis. Treatment depends on acuity, severity, clinical presentation, and etiology. Approximately 75% of patients admitted with myocarditis have an uncomplicated course, with a mortality rate of approximately 0%. In contrast, acute myocarditis that is complicated by acute heart failure or ventricular arrhythmias is associated with a 12% rate of either in-hospital mortality or need for heart transplant. Approximately 2% to 9% of patients have hemodynamic instability, characterized by inability to maintain adequate end-organ perfusion, and require inotropic agents, or mechanical circulatory devices, such as extracorporeal life support, to facilitate functional recovery. These patients have an approximately 28% rate of mortality or heart transplant at 60 days. Immunosuppression (eg, corticosteroids) is appropriate for patients who have myocarditis characterized by eosinophilic or giant cell myocardial infiltrations or due to systemic autoimmune disorders. However, the specific immune cells that should be targeted to improve outcomes in patients with myocarditis remain unclear. Conclusions and Relevance Acute myocarditis affects approximately 4 to 14 per 100 000 people per year. First-line therapy depends on acuity, severity, clinical presentation, and etiology and includes supportive care. While corticosteroids are often used for specific forms of myocarditis (eg, eosinophilic or giant cell infiltrations), this practice is based on anecdotal evidence, and randomized clinical trials of optimal therapeutic interventions for acute myocarditis are needed.
Long noncoding RNA HITT coordinates with RGS2 to inhibit PD-L1 translation in T cell immunity
Authors: Qingyu Lin, Tong Liu, Xingwen Wang, Guixue Hou, Zhiyuan Xiang, Wenxin Zhang, Shanliang Zheng, Dong Zhao, Qibin Leng, Xiaoshi Zhang, Minqiao Lu, Tianqi Guan, Hao Liu, Ying Hu
Journal: Journal of Clinical Investigation (2023)

Programmed cell death ligand 1 (PD-L1) is an immune checkpoint protein frequently expressed in human cancers that contributes to immune evasion through its binding to PD-1 on activated T cells. Unveiling the mechanisms underlying PD-L1 expression is essential for understanding the impact of the immunosuppressive microenvironment and is also crucial for the purpose of reboosting antitumor immunity. However, how PD-L1 is regulated, particularly at translational levels, remains largely unknown. Here, we discovered that a long noncoding RNA (lncRNA), HIF-1α inhibitor at translation level (HITT), was transactivated by E2F transcription factor 1 (E2F1) under IFN-γ stimulation. It coordinated with regulator of G protein signaling 2 (RGS2) in binding to the 5' UTR of PD-L1, resulting in reduced PD-L1 translation. HITT expression enhanced T cell-mediated cytotoxicity both in vitro and in vivo in a PD-L1-dependent manner. The clinical correlation between HITT/PD-L1 and RGS2/PD-L1 expression was also detected in breast cancer tissues. Together, these findings demonstrate the role of HITT in antitumor T cell immunity, highlighting activation of HITT as a potential therapeutic strategy for enhancing cancer immunotherapy.
Starburst amacrine cells, involved in visual motion perception, loose their synaptic input from dopaminergic amacrine cells and degenerate in Parkinson’s disease patients
Authors: Xavier Sánchez-Sáez, Isabel Ortuño-Lizarán, Carla Sánchez-Castillo, Pedro Lax, Nicolás Cuenca
Journal: Translational Neurodegeneration (2023)

Abstract Background The main clinical symptoms characteristic of Parkinson’s disease (PD) are bradykinesia, tremor, and other motor deficits. However, non-motor symptoms, such as visual disturbances, can be identified at early stages of the disease. One of these symptoms is the impairment of visual motion perception. Hence, we sought to determine if the starburst amacrine cells, which are the main cellular type involved in motion direction selectivity, are degenerated in PD and if the dopaminergic system is related to this degeneration. Methods Human eyes from control ( n = 10) and PD ( n = 9) donors were available for this study. Using immunohistochemistry and confocal microscopy, we quantified starburst amacrine cell density (choline acetyltransferase [ChAT]-positive cells) and the relationship between these cells and dopaminergic amacrine cells (tyrosine hydroxylase-positive cells and vesicular monoamine transporter-2-positive presynapses) in cross-sections and wholemount retinas. Results First, we found two different ChAT amacrine populations in the human retina that presented different ChAT immunoreactivity intensity and different expression of calcium-binding proteins. Both populations are affected in PD and their density is reduced compared to controls. Also, we report, for the first time, synaptic contacts between dopaminergic amacrine cells and ChAT-positive cells in the human retina. We found that, in PD retinas, there is a reduction of the dopaminergic synaptic contacts into ChAT cells. Conclusions Taken together, this work indicates degeneration of starburst amacrine cells in PD related to dopaminergic degeneration and that dopaminergic amacrine cells could modulate the function of starburst amacrine cells. Since motion perception circuitries are affected in PD, their assessment using visual tests could provide new insights into the diagnosis of PD.
Cellular states are coupled to genomic and viral heterogeneity in HPV-related oropharyngeal carcinoma
Authors: Sidharth V. Puram, Michael Mints, Ananya Pal, Zongtai Qi, Ashley Reeb, Kyla Gelev, Thomas F. Barrett, Sophie Gerndt, Ping Liu, Anuraag S. Parikh, Salma Ramadan, Travis Law, Edmund A. Mroz, James W. Rocco, Doug Adkins, Wade L. Thorstad, Hiram A. Gay, Li Ding, Randal C. Paniello, Patrik Pipkorn, Ryan S. Jackson, Xiaowei Wang, Angela Mazul, Rebecca Chernock, Jose P. Zevallos, Jessica Silva-Fisher, Itay Tirosh
Journal: Nature Genetics (2023)
Genetic effects on the timing of parturition and links to fetal birth weight
Authors: Pol Solé-Navais, Christopher Flatley, Valgerdur Steinthorsdottir, Marc Vaudel, Julius Juodakis, Jing Chen, Triin Laisk, Abigail L LaBella, David Westergaard, Jonas Bacelis, Ben Brumpton, Line Skotte, Maria C Borges, Øyvind Helgeland, Anubha Mahajan, Matthias Wielscher, Frederick Lin, Catherine Briggs, Carol A Wang, Gunn-Helen Moen, Robin N Beaumont, Jonathan P Bradfield, Abin Abraham, Gudmar Thorleifsson, Maiken E Gabrielsen, Sisse R Ostrowski, Dominika Modzelewska, Ellen A Nohr, Elina Hypponen, Amit Srivastava, Octavious Talbot, Catherine Allard, Scott M Williams, Ramkumar Menon, Beverley M Shields, Gardar Sveinbjornsson, Huan Xu, Mads Melbye, William Lowe, Luigi Bouchard, Emily Oken, Ole B Pedersen, Daniel F Gudbjartsson, Christian Erikstrup, Erik Sørensen, Rolv T Lie, Kari Teramo, Mikko Hallman, Thorhildur Juliusdottir, Hakon Hakonarson, Henrik Ullum, Andrew T Hattersley, Line Sletner, Mario Merialdi, Sheryl L Rifas-Shiman, Thora Steingrimsdottir, Denise Scholtens, Christine Power, Jane West, Mette Nyegaard, John A Capra, Anne H Skogholt, Per Magnus, Ole A Andreassen, Unnur Thorsteinsdottir, Struan F A Grant, Elisabeth Qvigstad, Craig E Pennell, Marie-France Hivert, Geoffrey M Hayes, Marjo-Riitta Jarvelin, Mark I McCarthy, Deborah A Lawlor, Henriette S Nielsen, Reedik Mägi, Antonis Rokas, Kristian Hveem, Kari Stefansson, Bjarke Feenstra, Pål Njolstad, Louis J Muglia, Rachel M Freathy, Stefan Johansson, Ge Zhang, Bo Jacobsson
Journal: Nature Genetics (2023)

The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal-fetal relationship between gestational duration and birth weight.
Neoadjuvant enoblituzumab in localized prostate cancer: a single-arm, phase 2 trial
Authors: Eugene Shenderov, Angelo M. De Marzo, Tamara L. Lotan, Hao Wang, Sin Chan, Su Jin Lim, Hongkai Ji, Mohamad E. Allaf, Carolyn Chapman, Paul A. Moore, Francine Chen, Kristina Sorg, Andrew M. White, Sarah E. Church, Briana Hudson, Paul A. Fields, Shaohui Hu, Samuel R. Denmeade, Kenneth J. Pienta, Christian P. Pavlovich, Ashley E. Ross, Charles G. Drake, Drew M. Pardoll, Emmanuel S. Antonarakis
Journal: Nature Medicine (2023)
Promoting Health Equity Through Preventing or Mitigating the Effects of Gentrification: A Theoretical and Methodological Guide
Authors: Helen V.S. Cole, Isabelle Anguelovski, Margarita Triguero-Mas, Roshanak Mehdipanah, Mariana Arcaya
Journal: Annual Review of Public Health (2023)

Public health researchers are increasingly questioning the consequences of gentrification for population health and health equity, as witnessed in the rapid increase in public health publications on the health (equity) effects of gentrification. Despite methodological challenges, and mixed results from existing quantitative research, qualitative evidence to date points to the role of gentrification processes in exacerbating health inequities. Here we discuss past methodological and theoretical challenges in integrating the study of gentrification with public health research. We suggest taking an interdisciplinary approach, considering the conceptualization of gentrification in measurement techniques and conceiving this process as a direct exposure or as a part of broader neighborhood changes. Finally, we discuss existingpolicy approaches to mitigating and preventing gentrification and how these could be evaluated for effectiveness and as public health promotion and specifically as interventions to promote health equity.
Decoding Hypertension Through Primary Aldosteronism
Authors: Braxton D. Mitchell, Hilary B. Whitlatch
Journal: Circulation (2023)

rimary aldosteronism (PA) is one of the most common causes of secondary hypertension.It is usually caused by idiopathic adrenal hyperplasia or aldosterone-producing adenomas (APAs), and it is a particularly morbid form of secondary hypertension.Compared with those with essential hypertension, patients with PA are at substantially higher risk of stroke, coronary artery disease, atrial fibrillation, and heart failure. 1 PA has also been shown to increase the risk of diabetes, metabolic syndrome, and left ventricular hypertrophy. 1 Identifying this subgroup of patients with hypertension would allow more aggressive management of their cardiometabolic risk.
Multi-omics for biomarker approaches in the diagnostic evaluation and management of abdominal pain and irritable bowel syndrome: what lies ahead
Authors: Andrea Shin, Purna C. Kashyap
Journal: Gut Microbes (2023)

Reliable biomarkers for common disorders of gut–brain interaction characterized by abdominal pain, including irritable bowel syndrome (IBS), are critically needed to enhance care and develop individualized therapies. The dynamic and heterogeneous nature of the pathophysiological mechanisms that underlie visceral hypersensitivity have challenged successful biomarker development. Consequently, effective therapies for pain in IBS are lacking. However, recent advances in modern omics technologies offer new opportunities to acquire deep biological insights into mechanisms of pain and nociception. Newer methods for large-scale data integration of complementary omics approaches have further expanded our ability to build a holistic understanding of complex biological networks and their co-contributions to abdominal pain. Here, we review the mechanisms of visceral hypersensitivity, focusing on IBS. We discuss candidate biomarkers for pain in IBS identified through single omics studies and summarize emerging multi-omics approaches for developing novel biomarkers that may transform clinical care for patients with IBS and abdominal pain.
Obstacles to implement machine perfusion technology in routine clinical practice of transplantation: Why are we not there yet?
Authors: Mauricio Flores Carvalho, Yuri L. Boteon, James V. Guarrera, Pranjal R. Modi, Laura Lladó, Georg Lurje, Mureo Kasahara, Philipp Dutkowski, Andrea Schlegel
Journal: Hepatology (2023)

Machine perfusion of solid human organs is an old technique, and the basic principles were presented as early as 1855 by Claude Barnard. More than 50 years ago, the first perfusion system was used in clinical kidney transplantation. Despite the well-known benefits of dynamic organ preservation and significant medical and technical development in the last decades, perfusion devices are still not in routine use. This article describes the various challenges to implement this technology in practice, critically analyzing the role of all involved stakeholders, including clinicians, hospitals, regulatory, and industry, on the background of regional differences worldwide. The clinical need for this technology is discussed first, followed by the current status of research and the impact of costs and regulations. Considering the need for strong collaborations between clinical users, regulatory bodies, and industry, integrated road maps and pathways required to achieve a wider implementation are presented. The role of research development, clear regulatory pathways, and the need for more flexible reimbursement schemes is discussed together with potential solutions to address the most relevant hurdles. This article paints an overall picture of the current liver perfusion landscape and highlights the role of clinical, regulatory, and financial stakeholders worldwide.
Ferroptosis in hepatocellular carcinoma: from bench to bedside
Authors: Daolin Tang, Guido Kroemer, Rui Kang
Journal: Hepatology (2023)

The most widespread type of liver cancer, HCC, is associated with disabled cellular death pathways. Despite therapeutic advancements, resistance to current systemic treatments (including sorafenib) compromises the prognosis of patients with HCC, driving the search for agents that might target novel cell death pathways. Ferroptosis, a form of iron-mediated nonapoptotic cell death, has gained considerable attention as a potential target for cancer therapy, especially in HCC. The role of ferroptosis in HCC is complex and diverse. On one hand, ferroptosis can contribute to the progression of HCC through its involvement in both acute and chronic liver conditions. In contrast, having ferroptosis affect HCC cells might be desirable. This review examines the role of ferroptosis in HCC from cellular, animal, and human perspectives while examining its mechanisms, regulation, biomarkers, and clinical implications.
Role of sex in liver tumor occurrence and clinical outcomes: A comprehensive review
Authors: Pierluigi Toniutto, Sarah Shalaby, Laura Mameli, Filomena Morisco, Martina Gambato, Valentina Cossiga, Maria Guarino, Fabio Marra, Maurizia R. Brunetto, Patrizia Burra, Erica Villa
Journal: Hepatology (2023)

Clinical research on sex-based differences in the manifestations, pathophysiology, and prevalence of several diseases, including those affecting the liver, has expanded considerably in recent years. Increasing evidence suggests that liver diseases develop, progress, and respond to treatment differently depending on the sex. These observations support the concept that the liver is a sexually dimorphic organ in which estrogen and androgen receptors are present, which results in disparities between men and women in liver gene expression patterns, immune responses, and the progression of liver damage, including the propensity to develop liver malignancies. Sex hormones play protective or deleterious roles depending on the patient’s sex, the severity of the underlying disease, and the nature of precipitating factors. Moreover, obesity, alcohol consumption, and active smoking, as well as social determinants of liver diseases leading to sex-related inequalities, may interact strongly with hormone-related mechanisms of liver damage. Drug-induced liver injury, viral hepatitis, and metabolic liver diseases are influenced by the status of sex hormones. Available data on the roles of sex hormones and gender differences in liver tumor occurrence and clinical outcomes are conflicting. Here, we critically review the main gender-based differences in the molecular mechanisms associated with liver carcinogenesis and the prevalence, prognosis, and treatment of primary and metastatic liver tumors.
The Negative Influence of Baseline Cell-free DNA on Long-term Survival in DLBCL Depends on Frontline Treatment Intensity
Authors: Fabienne Desmots, Delphine Rossille, Mikael Roussel, Céline Pangault, Laetitia Louarn, Mylène De Saint Jore, Steven Le Gouill, Krimo Bouabdallah, Vincent Delwail, Remy Gressin, Jérôme Cornillon, Gandhi Damaj, Hervé Maisonneuve, Diane Damotte, Françoise Kraeber-Bodere, Thierry Lamy, Marie-Cécile Parrens, Noël Milpied, Thierry Fest
Journal: Clinical Cancer Research (2023)

Abstract Purpose: This study aims to investigate the relationship between the intensity of the initial treatment given to patients with de novo diffuse large B-cell lymphoma (DLBCL) and the impact of their baseline cell-free DNA (cfDNA) levels on their long-term survival. Experimental Design: The GOELAMS 075 randomized clinical trial compared rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with high-dose R-chemotherapy plus autologous stem cell transplantation (R-HDT) for patients aged ≤60. An interim PET assessment was used to refer patients for salvage therapy. With a median follow-up of more than 5.8 years, we analyzed the effects of the treatment arm, salvage therapy, and cfDNA level at diagnosis on overall survival (OS). Results: In a representative group of 123 patients, a high cfDNA concentration (&amp;gt;55 ng/mL) at diagnosis was associated with poor clinical prognostic factors and constituted a prognostic marker, independently of the age-adjusted International Prognostic Index. A cfDNA level above a threshold value of 55 ng/mL at diagnosis was associated with significantly worse OS. In an intention-to-treat analysis, high-cfDNA R-CHOP patients (but not high-cfDNA R-HDT patients) had worse OS [HR (95% confidence interval), 3.99 (1.98–10.74); P = 0.006]. In patients with high cfDNA levels, salvage therapy and transplantation were associated with a significantly higher OS rate. Among 50 patients with complete response 6 months after the end of treatment, for 11 of 24 R-CHOP patients, the cfDNA did not fall back to normal values. Conclusions: In this randomized clinical trial, intensive regimens mitigated the negative influence of high cfDNA levels in de novo DLBCL, relative to R-CHOP.
Materialized Oppression in Inpatient Psychiatric Unit Design
Authors: Grayson Holt, Jeffrey Zabinski, Topaz Sampson-Mills
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Materialized Oppression in Medical Tools and Technologies Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
HPV Integration Can Drive the Formation of Virus–Host Extrachromosomal DNA in Tumors
Authors: Alison A. McBride, Elizabeth A. White
Journal: Cancer Discovery (2023)

Human papillomavirus (HPV)-positive cancer cells contain virus and host DNA and exhibit marked genome instability. In this issue of Cancer Discovery, Akagi and colleagues characterize the remarkably complex landscape of virus-host DNA molecules in HPV-positive cells, providing evidence for diverse integrated and extrachromosomal virus-host hybrid DNAs with the potential to drive clonal evolution. See related article by Akagi et al., p. 910 (4).
TrEMOLO: accurate transposable element allele frequency estimation using long-read sequencing data combining assembly and mapping-based approaches
Authors: Mourdas Mohamed, François Sabot, Marion Varoqui, Bruno Mugat, Katell Audouin, Alain Pélisson, Anna-Sophie Fiston-Lavier, Séverine Chambeyron
Journal: Genome biology (2023)

Transposable Element MOnitoring with LOng-reads (TrEMOLO) is a new software that combines assembly- and mapping-based approaches to robustly detect genetic elements called transposable elements (TEs). Using high- or low-quality genome assemblies, TrEMOLO can detect most TE insertions and deletions and estimate their allele frequency in populations. Benchmarking with simulated data revealed that TrEMOLO outperforms other state-of-the-art computational tools. TE detection and frequency estimation by TrEMOLO were validated using simulated and experimental datasets. Therefore, TrEMOLO is a comprehensive and suitable tool to accurately study TE dynamics. TrEMOLO is available under GNU GPL3.0 at https://github.com/DrosophilaGenomeEvolution/TrEMOLO .
Editor's Note: Dual Targeting of the Akt/mTOR Signaling Pathway Inhibits Castration-Resistant Prostate Cancer in a Genetically Engineered Mouse Model
Authors: Nicola Floc'h, Carolyn Waugh Kinkade, Takashi Kobayashi, Alvaro Aytes, Celine Lefebvre, Antonina Mitrofanova, Robert D. Cardiff, Andrea Califano, Michael M. Shen, Cory Abate-Shen
Journal: Cancer Research (2023)

The editors are publishing this note to alert readers to concerns about this article (1). In Fig. 3V, there is splicing in the images for pAKTS473 and for pS6S235/236. In Fig. 4, the same image was used for the Actin Western blot analysis in Fig. 4A for PC3 cells and in Fig. 4C, as they were from the same experiment; however, this was not indicated in the figure legend.
Moral Distress in Military Medicine: Toward Analysis of, and Approach to Measurement, Prevention and Care
Authors: Megan Applewhite, James Giordano
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Moral Distress: What Are We Measuring? Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Control of mitochondria-associated endoplasmic reticulum membranes by protein S-palmitoylation: Novel therapeutic targets for neurodegenerative diseases
Authors: Qiangqiang He, Meiyu Qu, Tingyu Shen, Jiakun Su, Yana Xu, Chengyun Xu, Muhammad Qasim Barkat, Jibao Cai, Haibin Zhu, Ling-Hui Zeng, Ximei Wu
Journal: Ageing Research Reviews (2023)